The pharmacologic and toxicologic effects of marihuana are generally attributed to delta-9-tetrahydrocannabinol. However, other cannabinoids may also play an important role in determining the overall effects associated with marihuana. We therefore propose to extend our study of the toxicology of cannabinoids to include cannabinol and cannabichromene, alone and in combination with delta-9-tetrahydrocannabinol. The effects of these drugs will be examined in animal models as well as human subjects. Besides the cannabinoids, marihuana smoke contains other compounds which may influence the activity of marihuana. Thus, various fractions of marihuana smoke condensate will be analyzed to determine their respective pharmaco-toxic properties. The therapeutic potential of the cannabinoids is intimately related to their toxicity. It is therefore reasonable to examine the effect of cannabinoids alone and in combination with other drugs which are misused and which also have therapeutic value. Experiments will be conducted to examine the effects of selected cannabinoids in combination with benzodiazepines and a new antidepressant and possible alcohol antagonist. Further studies are proposed to investigate the effect of cannabinoids on airway mechanics in animals. An animal model will also be used to evaluate the efficacy of delta-9-tetrahydrocannabinol in the treatment of asthma.